RESUMEN
Understanding the genetic diversity, extent and distribution of variant forms of Plasmodium vivax parasites is crucial in the development of effective control measures and in Orissa, a hyperendemic state in the eastern part of India, the polymorphic nature of P. vivax isolates is largely lacking. The result of the study analyzing two highly polymorphic single copy genes for P. vivax circumsporozoite protein (pvcs) and P. vivax merozoite surface protein 3α (pvmsp3α) shows that the parasite population is highly heterogenous (33 distinct genotype from 35 isolates) in Orissa. However, the observation of the multiplicity of infection value of 1.34 and high frequency distribution of certain genotype with respect to individual marker (the VK247b allele with a frequency of 0.37; VK210e with 0.25 and VK210c with 0.14) suggests that the parasite population are likely to be under selective pressure and may either be due to preferential production of sporozoites carrying these variants in the available anopheline mosquito species of the state or selection of particular genotypes by host immune pressure. Moreover, although P. vivax in South-East Asia indicates an overall predominance of VK210 which is thought to be the best adapted variant of pvcs repeat type, the almost equal prevalence of both repeat type of pvcs; VK210 and VK247 in the present study is unexpected and needs further study for clarification.
Asunto(s)
Variación Genética , Malaria Falciparum/epidemiología , Malaria Vivax/epidemiología , Malaria Vivax/parasitología , Plasmodium vivax/clasificación , Plasmodium vivax/genética , Antígenos de Protozoos/genética , ADN Protozoario/genética , Frecuencia de los Genes , Humanos , India/epidemiología , Proteínas Protozoarias/genética , Selección GenéticaRESUMEN
To assess the hypothesis that nitric oxide (NO) is critical in the pathogenesis of cerebral malaria, we analyzed those single nucleotide polymorphisms (SNPs) and microsatellite (MS) of the promoter region of inducible nitric oxide synthase (iNOS) gene which are known to enhance the NO production in vivo. A total of 428 (204 severe, 224 mild) adult patients living in the eastern part of India were analyzed. The single nucleotide substitutions -954G-->C was found to be very rare, and -1173C-->T was absent in this population. But interestingly, longer forms of MS were found to be significantly associated with severe malaria (OR = 2.89, 95% CI = 1.955-4.295, P < 0.0001), and the linear regression analysis revealed that the risk of severe malaria significantly increases as the summed repeat number in an individual increase (OR = 1.16, P = 0.0013). Further, the median plasma level of nitrate/nitrite (NOx) was observed to be high in mild patients compared to severe patients, and the level of parasitemia was significantly low among mild patients than severe ones. These findings suggest that the CCTTT repeats in iNOS may play a key role in the pathogenesis of severe malaria.
Asunto(s)
Malaria Cerebral/genética , Malaria Falciparum/genética , Repeticiones de Microsatélite , Óxido Nítrico Sintasa de Tipo II/genética , Plasmodium falciparum/inmunología , Polimorfismo Genético , Regiones Promotoras Genéticas , Adulto , Animales , Humanos , India , Malaria Cerebral/inmunología , Malaria Falciparum/inmunología , Óxido Nítrico/sangre , Parasitemia , Adulto JovenRESUMEN
Light microscopy, the mainstay of malaria diagnosis in epidemiologic studies, exhibits limited sensitivity for detecting low level infections and often under-estimates the frequency of mixed Plasmodium species infections. To overcome these shortcomings we performed the PCR method for detection and identification of Plasmodium species in blood specimens from 242 individuals collected during the peak season of malaria incidence (July-October). Malaria prevalence was 81.4% and 43.4% by PCR and microscopy respectively. Moreover, while PCR detected Plasmodium malariae DNA in 108 (44.6%), microscopic examination detected only 20 (8.3%) individuals parasitized with this species. Further data analysis revealed an independent random distribution pattern of parasites irrespective of age groups (0-5 yrs, chi-square7df=2.77, P>0.95; 6-15 yrs, chi-square7df=4.82, P>0.50; >15 yrs, chi-square7df=4.4, P>0.70) and sexes (for male chi-square7df=2.48, P>0.95; for female, chi-square7df=1.85, P>0.95). However, although the parasite distribution is random irrespective of sex, females had more P. malariae infections (P=0.004, OR=2.312, 95% CI=1.3-4.1). Our study demonstrates that the parasite distribution in Orissa is random with substantially higher prevalence of P.malariae than previously suspected and this may be seasonal. A study of the bionomics of vector(s) responsible for P. malariae transmission in Orissa is needed to provide information for the control of malaria in the state.